ABSTRACT Unintentional fatal drug overdose (OD) is now the 2nd leading cause of accidental death in the general population. Fatal OD from opioid analgesics specifically has increased over 400% between 1999 and 2008, and nonfatal overdose occurs at a rate 3-7 greater than fatal OD (1-4). Unintentional opioid OD is a public health crisis in several societal populations including drug users, patients being treated for chronic pain, elderly individuals, adolescents, and children (1-3; 6-10). Educational interventions have been developed to increase knowledge regarding opioid OD risk factors, symptoms, and appropriate responses, however, no randomized controlled evaluations of these interventions have been conducted. Within-subject evaluations report immediate and sustained increases in participant knowledge and behavior change (13-17), yet these programs suffer from limitations that may limit their widespread dissemination. Thus, there is an urgent, critical need to develop an opioid OD educational intervention that can be accessed by a broad audience, and produces immediate and sustained gains in knowledge in an easily administered and cost-effective way. We have expertise in developing computerized training curriculum for drug users and are proposing to use an innovative and proprietary computer training program developed by our group to create a web-based, computerized, interactive, opioid OD education training program that will incorporate multi-media learning components and fluency training to produce knowledge gains. This proposal is an R21 and a Stage 1 Early Therapy Development proposal for the NIDA Behavioral Therapies Development Program. Phase 1 of this study will be to develop a computerized opioid OD prevention program that incorporates features of direct instruction and operant conditioning to promote immediate and sustained knowledge gain. Phase 2 will be a randomized, controlled evaluation of the intervention against two control interventions. Participants will be recruited from a brief inpatient detoxification (n=60), will receive the intervention immediately upon completing the detoxification, and will complete 2 follow-up visits to evaluate sustained knowledge. The primary outcome will be percent change from baseline on a knowledge test that is administered pre and post intervention, and at the 1 and 3 month follow-up visits. Secondary outcomes will include self-reported behavior change and participant acceptance of the intervention. The rationale and public health benefit of this research cannot be understated- this project will make available a brief, empirically-supported intervention that can be administered quickly and easily within hundreds of settings (e.g., treatment centers, prisons and jails, needle exchange centers, primary care offices, schools), and to diverse patient populations (e.g., drug users, chronic pain patients, elderly, student, children, parents). These outcomes are expected to have a positive impact because they will provide cheap, easily-administered intervention strategy that will help reduce the current national epidemic of opioid OD, and will expand the use of computerized interventions to address public health issues more broadly.